1. Acute myeloid leukemia
mutations that impede myeloblast differentiation, and increases proliferation,  
Accumulated blasts leads to marrow failure (myelophthisic anemia)
AML occurs at all ages, but the incidence rises throughout life
Diagnosis of AML: blast count is ≥ 20% of bone marrow cells or peripheral blood

2. FAB-Classification M1: AML without maturation (blasts ≥ 80%)
M2: AML with maturation (blasts 20-80%)
M3: Acute promyelocytic leukemia
M4: Acute myelomonocytic leukemia
M5: Acute monocytic leukemia
M6: Acute erythrocytic leukemia
M7: Acute megakaryocytic leukemia

3. WHO-Classification
AML-recurrent cytogenetic abnormality: t(8:21), t(15:17), inversion11
AML-Myelodysplasia related changes (complicates MDS)
Therapy-related myeloid neoplasm
AML- not otherwise specified

4. Morphology
Myeloblasts have delicate nuclear chromatin, two to four nucleoli, and abundant cytoplasm
Auer rods: distinctive needle-like azurophilic granules (peroxidase), sometimes seen
Blasts commonly appear in peripheral blood
Myeloblasts express CD34 and myeloperoxidase

5. AML: myeloblasts are large, high N/C ratio, prominent nucleoli

6. Acute promyelocytic leukemia
FAB-M3
WHO: AML-t(15:17), PML-RARA gene fusion
Promyelocytic leukemia gene – retinoic acid receptor alpha
New protein binds cell DNA, blocking maturation (reversed by vitamin A and arsenic)
Cells are arrested at promyelocytic stage, showing prominent cytoplasmic granules and Auer rods
Malignant promyelocytes secrete tissue factor, activating thrombin, initiating coagulation cascade (disseminated intravascular coagulation-DIC)

7. Acute promyelocytic leukemia-bone marrow aspirate
Acute promyelocytic leukemia-bone marrow aspirate. The neoplastic promyelocytes have abnormally coarse and numerous azurophilic granules. Other characteristic findings include the presence of several cells with bilobed nuclei and a cell in the center of the field that contains multiple needle-like Auer rods

8. Acute monocytic leukemia
FAB-M5
Monocytes + promonocytes + monoblasts ≥80% of BM cells
Extramedullary masses of leukemia are common (skin, gum, CNS)
Monoblasts are large, with abundant and slightly basophilic cytoplasm, round central nuclei, prominent nucleoli, no granules of Auer rods

10. Clinical manifestations
Bone pain
Bleeding
Anemia
Infections
Solid organ damage

11. Lymphoid neoplasms

12. Lymphoma Neoplastic disorders originate from B or T lymphocytes
Most commonly arise in lymph nodes
If circulates peripheral blood or bone marrow, it is called lymphoid leukemia
They vary widely in their clinical presentation and behavior, low or high-grade lymphomas
Generally classified as Hodgkin and non-Hodgkin lymphomas
Risk factors: immune suppression, chronic inflammation, EBV, HHV8, HTLV1

14. Diagnosis Large lymph nodes (>2 cm)
Patients may have B-symptoms: fever, night sweating, weight loss, anorexia
Immune suppression
High LDH level
Microscopic: Abnormal architecture
Overgrowth of B or T-cells
B-cells express CD19, CD20
T-cells express CD2, CD3, CD5
Lymphoblasts express Terminal deoxynucleotidyl transferase (TdT) enzyme

15. Acute Lymphoblastic Leukemia/ Lymphoma
An aggressive, high-grade type of leukemia/lymphoma
Arises from precursor lymphoid cells (lymphoblasts), B or T
B-ALL is the most common cancer is children, arises from BM, affecting blood, and sometimes LNs
T-ALL occurs mainly in male adolescents, arises from thymus, then affecting blood, BM and other tissues
Lymphoblasts develop mutations in transcription genes which regulate both lymphocyte differentiation and proliferation
Blasts express Terminal deoxynucleotidyl transferase (TdT)
Lymphoblasts ≥ 20% BM cells, causing myelophthisic anemia
When disease manifests in lymph nodes, called lymphoblastic lymphoma

16. Clinical features Abrupt, stormy onset of symptoms
Patients have fever, anemia, bleeding, bone pain
Lymphoblasts tend to disseminate into tissues: Generalized lymphadenopathy, splenomegaly, hepatomegaly, brain, testis (in contrast to AML)

17. Morphology: lymphoblasts have fine chromatin, minimal agranular cytoplasm

18. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Low grade B-cell lymphoma
Cells are small, round, mature looking similar to normal lymphocytes
Affects BM and blood (CLL), or LN (SLL)
Bcl2 (anti-apoptotic protein) is up-regulated
Express CD5
The most common leukemia in elderly
Causes derangement in immune system (hypogammaglobulinemia), or auto AB-hemolytic anemia
Indolent course, stays stable for years
10% transforms to high-grade lymphoma

19. A: Low-power view shows diffuse effacement of nodal architecture. 
B, At high power, a majority of the tumor cells have the appearance of small, round lymphocytes, with scattered larger cells: "prolymphocyte," that have a central nucleolus

20. CLL: leukemia cells are small in size, resemble normal lymphocytes
CLL: leukemia cells are small in size, resemble normal lymphocytes. Burst “smudge” cells are commonly seen